OVERVIEW

The module aims at developing the fundamental notions of organic chemistry apprehended in Organic Chemistry 1, Laboratory of Organic Chemistry and Organic Chemistry 2, by the introduction of new subjects or deepening some arguments previously treated in a preliminary way. The module aims at improving the understanding of reaction mechanisms and in making the student able to design a synthesis.

AIMS AND CONTENT

LEARNING OUTCOMES

The student will deepen various aspects of organic chemistry not yet treated in previous modules (in particular C-C bond forming reactions) and will be guided to reach a good capacity to understand retrosynthetic strategies, design simple syntheses of aliphatica and aromatic compounds, to interpret reaction mechanisms and the strategies used to corroborate them.

AIMS AND LEARNING OUTCOMES

The student will deepen various aspects of organic cgemistry not yet treated in previous modules (in particular C-C bond forming reactions) and will be guided to reach a good capacity to understand retrosynthetic strategies, design simple syntheses of aliphatica and aromatic compounds, to interpret reaction mechanisms and the strategies used to corroborate them.

PREREQUISITES

For an optimal fruition of the course, the knowledge of the basic notions of  Organic Chemistry 1 and 2 and of the Laboratory of Organic Chemistry is essential.

TEACHING METHODS

The module includes mainly frontal lessons, with the prevalent use of slides. However, a set of retrosynthesis exercises will be provided and the students may access a recording of the described solutions of these exercises by the teacher. All lessons and exercise solutions will be in italian

SYLLABUS/CONTENT

1. C-C and C=C bond formation (8 hours)
   • Homoaldol reaction and homocrotonic condensation under acid or basic catalysis
   • Cross aldol reactions.
   • Allyl derivatives as synthetic equivalents of aldehydes
   • Claisen, Dieckmann, Darzens and Reformatsky reactions
   • Active methylene compounds. malonic and acetoacetic synthesis.
   • Knoevenagel reaction.
   • Reactions of α,β-unsaturated systems: kinetic and thermodynamic control. Addition of organometal compounds (Cu, Ce) and selective reductions.
   • Michael reactions with active methylene compounds.
   • Robinson annulation.
   • Use of enamines.
   • Nitroaldol reaction. Trasformations of nitro group.
   • Aldol and Claisen reactions in biology.
   • Wittig and Horner-Wadsworth-Emmons reactions.
   • Synthesis of α,β-unsaturated systems: summary
   • Cross-coupling reactions (hints).
2. Chemistry of aromatic and heteroaromatic compounds (6 hours)
   • Polycyclic aromatic hydrocarbons. Naming.
   • Naphthalene: properties and reactions.
   • Anthracene and phenanthrene
   • Review of main electrophilic and nucleophilic substitutions. Mechanism of Sandmeyer reactions. Vicarious nucleophilic substitution (Chichibabin).
   • Formylation and carboxylation reaction.
   • Benzylic oxidations.
   • Hantzsch-Widmann nomenclature of heterocyclic compounds.
3. Synthesis design: aromatic compounds (5 hours)
   • General concepts: linear, convergent synthesis. Total synthesis and semi-synthesis. Retrosynthetic approach. 
   • Synthetic equivalence.
   • Strategies for the synthesis of polysubstituted aromatic compounds. Removable groups. Clemmensen and Wolff-Kishner reactions.
   • Exercises on the synthesis of aromatic compounds.
4. Synthesis design: aliphatic compounds (6 hours)
   • Synthesis of C-X bonds.
   • Synthesis of amines
   • Retrosynthesis of C-C bonds (1 functional group).
     • Alcohols
     • Ketones.
     • Carboxylic derivatives
     • Alkenes
   • Retrosynthesis of C-C bonds (2 functional groups). Logical and illogical disconnections
   • Logical disconnections: synthesis of 1,3 and 1,5 derivatives
   • Synthesis of 1,3 and 1,5 derivatives:
     • Use of alpha-halocarbonyl compounds: alpha-halogenation under acid and basic conditions
     • Use of cyanide
     • Synthesis of 1,2-diols and epoxides. Pinacol reaction. Corey-Chaikovski reaction.
   • Synthesis design exercises
5. Protecting groups (5 hours)
   • Protection of amines. Peptide synthesis.
   • Protection of alcohols.
   • Protection of carbonyl compounds.
6. Synthesis of cyclic compounds (6 hours)
   • General issues of cyclization reactions
   • Examples of synthesis of 5-membered rings
   • Examples of synthesis of 6-membered rings
   • Hints on synthesis of 3- and 4-membered rings
   • Hints to olefin metatesis
   • Diels-Alder reaction.
   • 1,3-dipolar cycloadditions
7. Rearrangements (4 hours)
   • Carbocation rearrangement with 1,2 hydride shif
   • Pinacol rearrangement (also in tandem with Corey-Chaikovski reaction)
   • Wagner-Meerwein rearrangement
   • Baeyer-Villiger reaction
   • Hoffmann and Schmidt rearrangements
   • Arndt-Einstert rearrangement
   • Sigmatropic rearrangements: Cope and Claisen reactions
8. Diversity oriented synthesis (4 hours)
   • General concepts
   • Biological example of combinatorial synthesis: antibodies.
   • Multicomponent reactions
9. Reaction mechanisms (6 hours)
   • Non kinetical methods for delucidating a mechanism.
   • Kinetical methods for delucidating a mechanism.

RECOMMENDED READING/BIBLIOGRAPHY

The slides of the lessons will be available in pdf format on Aulaweb.

For the review / deepening of basic organic chemistry topics, the latest editions of the same texts recommended for the courses of Organic Chemistry I and II can be used; in particular:

-- Brown, Foote, Iverson, Anslyn - Organic Chemistry - EdiSES

-- Bruice - Organic Chemistry - EdiSES

-- Clayden, Greeves, Warren . Chimica Organica, seconda edizione - Piccin

-- Stuart Warren, Paul Wyatt - Organic synthesis - The Disconnection Approach, 2nd Edition - J. Wiley & Sons (2008).

The first three books are available also in english or in other languages.

TEACHERS AND EXAM BOARD

Exam Board

LUCA BANFI (President)

CHIARA LAMBRUSCHINI

RENATA RIVA (President Substitute)

LISA MONI (Substitute)

LESSONS

LESSONS START

From September 25, 2023

EXAMS

EXAM DESCRIPTION

The exam will be written and then oral.

The written exam will have two parts

1. specific questions that will generate an overall mark. According to the mark obtained the students will be admitted or not to the oral. The mark will also influence the final mark.
2. A retrosynthesis exercise.

The latter will not provide a mark. However, the exercise will be discussed during the oral exam. Obviously, if the student does not propose a suitable synthess, this will have an outcome on the oral evauation.

The oral exam will follow the written one, typically on the same very day.

If the student fails the oral exam or gives up, he/she will repeat the written exam in a later date.

The oral exam is an interview in front of the commission (of at least 2 persons). The student will necessarily use the blackboard and be able to draw chemical equations, formulas, and reaction mechanisms.

Important: there will be 7 possibility per year to give the exam. Further dates may be decided, but, if the student has formally attended the module in year 20xx/20xx+1, he/she will be allowed to take part to these additional exams only until the end of febrauary of 20xx+2.

Importante: verranno fissati 7 appelli per anno. Potranno essere concessi appelli straordinari solo dopo la fine del secondo semestre. Non verranno concessi però appelli straordinari agli studenti che, avendo avuto inserito l'insegnamento nel piano degli studi dell'anno 20xx/20xx+1, chiedano di sostenere l'esame dopo la fine di febbraio 20xx+2.

ASSESSMENT METHODS

During the interview, it is intended to ascertain, through the initial discussion of topics developed in the frontal lectures, the degree of understanding reached by the student as well as his reasoning ability in making connections between different parts of the program and in dealing with case studies related to those expressly treated in the program.

Exam schedule